Bipolar disorder is a severe heritable psychiatric illness affecting 1% of the general population. The age of onset is generally in the late teenage years or early adulthood. Very little is known about specific risk factors that influence the incidence and age of onset of this disorder. In 1988 the NIMH established a Genetics Initiative in bipolar disorder with the goal of identifying susceptibility genes; this collaboration has identified several hundred families with multiple cases of bipolar disorder. As 3 of the initial collaborating sites 'Indiana University, Johns Hopkins University, and Washington University at St Louis) we are now proposing to assess and follow adolescents, ages 12 -18 years, in these families. This will include offspring and nieces and nephews. This "at risk" group will be compared to a matched set of community comparison subjects. 300 study subjects and 300 controls will be studied using established diagnostic instruments (KSADS-PL) for the adolescents and the parents (DIGS). Other instruments to assess behavior, temperament, family environment, and substance use will be employed. The data will be stored in a database developed to facilitate longitudinal studies of clinical variables. Analyses will compare potential risk factors among the high-risk group and the controls. Annual follow-up of the high- risk group will begin in the second year of the study. It is hypothesized that 3 groups will be identified: 1) adolescents with behavioral symptoms or disorders who manifest early-onset bipolar disorder; 2) adolescents with anxiety symptoms or disorders who manifest later-onset bipolar disorder; and 3) adolescents with minor mood symptoms or disorders who manifest later-onset unipolar or bipolar disorder. The ethical implications of this research will be studied by examining the effects of participation and the effect on self-esteem due to high- risk status.